Chronic Stress in Youth Impairs Memory, May Cause Mental Illness

Zhen Yan, PhD

Published
March 7, 2012

For the first time, UB researchers have found proof at a
molecular level that chronic stress has a more powerful effect on
the brain during adolescence than adulthood, leading to memory
impairment and possibly triggering mental illness.

“If, based on this research, we can begin to target the glutamate system in a more specific and effective way, we might be able to develop better drugs to treat serious mental illness.”

Zhen Yan, PhD

Professor of physiology and biophysics

Their research, published in Neuron, shows how loss
of glutamate receptor expression and function in the prefrontal
cortex is causally linked to the negative effects of chronic
stress.

“Because dysfunction in the prefrontal cortex has been
implicated in stress-related mental illness, this research will
help further unravel how and why mental illnesses occur and how to
treat them,” says Zhen
Yan, PhD, professor of physiology and
biophysics.

Demonstrating a Causal Link to Cognitive Impairment

The UB researchers’ findings bolster an emerging
understanding that the glutamate system plays a key role in mental
illness and is thus critical to learning how to better treat
disorders like depression, anxiety and schizophrenia.

Their study involved male rats at an age corresponding to human
adolescence—a period when the brain is highly sensitive to
stress.

When the rats were exposed to repeated stress, they lost
glutamate receptor expression and function in the prefontal cortex,
a region of the brain that controls working memory, decision-making
and attention and doesn’t fully mature until age 25.

This loss significantly impaired the adolescent rats’
ability to remember and recognize objects they had previously
seen.

Similarly stressed adult rats, however, did not experience the
same cognitive deficit.

As a result, they have discovered that there may be a way to
prevent chronic stress’ detrimental effects.

Many antipsychotic drugs currently on the market do somehow
affect the glutamate system. Yan and her UB colleagues recently
published an
article in Molecular Pharmacology that showed how one of the
newer antipsychotics, lurasidone (marketed as Latuda), does just
that.

Yet a large number of these drugs also affect other important
neurotransmitter systems, Yan notes.

“If, based on this research, we can begin to target the
glutamate system in a more specific and effective way, we might be
able to develop better drugs to treat serious mental
illness.”

The research is especially significant because with some mental
disorders, such as schizophrenia, onset typically occurs in late
adolescence.

A Critical Need to Understand Stress at Molecular Level

While there have been many behavioral studies about stress,
understanding it at a molecular level is key to developing
strategies to prevent stress-induced behavioral deficits, Yan
notes.

“In the end, it has to be boiled down to molecules.
Without knowing why something happens at a molecular level, you
cannot do anything about it.”